The aim of this proposed research is to regulate the microenvironments (secondary coordination spheres) about metal ions to direct their chemistry. The approach utilizes the principles of molecular architecture that have been found in the active sites of metalloproteins. New modular tripodal ligands have been developed that create cavities around vacant binding sites in coordinatively unsaturated metal complexes. These ligands can position functional groups within the cavities to create specific chemical microenvironments about metal ions. We will investigate how cavity structure influences the functional and physical properties of metal complexes. Particular emphasis will be placed on studying the effects of the hydrogen bonds and the size of the cavities in directing chemistry at metal centers. Once these cavity-containing metal complexes are characterized both structurally and physically, they will be used to address how non-heme metalloproteins regulate dioxygen binding and activation, and utilize highly oxidized or radical intermediates in catalysis. Long term goals of this research include developing structure-function relationships in metal-assisted oxidative biomimetic catalysis. The systems outlined in this proposal offer an approach to designing new biomimetic metal complexes that have H-bonding cavities. The control of the molecular components that define the cavity structure permits the development of systems whose activity can be tailored to a particular reaction and class of substrates. The ability to fine-tune the molecular design of the external ligand binding site by varying the size and H-bonding groups is beneficial for regulating the microenvironment about active species. This allows for the systematic study of structure-function relationships that can lead to a fundamental understanding of metallobiochemical processes.